Composition for oral cavity

Abstract

This composition for the oral cavity contains an amino acid and a specific sugar. The specific sugar is at least one selected from lactose, 2'-fucosyllactose, galactose, raffinose, and a galactooligosaccharide.

Description

Oral composition

[0001] The present invention relates to an oral composition.

[0002] Many bacteria in the oral cavity exist either floating in the mouth or in bacterial aggregates called biofilms. Because biofilms are resistant to both physical and chemical agents, removing biofilms is more difficult than removing floating bacteria.

[0003] The mechanisms by which oral bacteria adhere to teeth and oral mucosal surfaces have long been studied, and many findings have been obtained. To effectively inhibit biofilm formation, it is believed that it is important to prevent early colonizing bacteria, which rapidly adhere to clean tooth surfaces and form initial plaque, from adhering to oral tissues. Early colonizing bacteria possess receptors that bind to salivary proteins, and binding of these receptors to specific salivary proteins is known to promote adhesion. These salivary proteins are broadly classified as proline-rich proteins and proline-rich glycoproteins. Representative bacteria that possess receptors for the former salivary proteins include Streptococcus mutans, Streptococcus gordonii, and Porphyromonas gingivalis, while representative bacteria that possess receptors for the latter salivary proteins include Staphylococcus aureus, Fusobacterium nucleatum, and Streptococcus oralis. Therefore, there is a need to develop a technology that has an effective anti-adhesion effect against these two groups of bacteria.For example, Patent Document 1 discloses a technology that uses a composition containing liposomes whose essential component is a hydrogenated phospholipid to prevent the adhesion and proliferation of bacteria such as Streptococcus mutans and Staphylococcus aureus to oral tissues.

[0004] Japanese Patent Application Laid-Open No. 2018-115179

[0005] As a result of intensive research by the present inventors, it was found that the concentration of Streptococcus oralis (hereinafter referred to as S. oralis) in the oral cavity is higher in people without a history of dental caries compared to people with a history of dental caries. This finding suggests that increasing the concentration of S. oralis in the oral cavity is important from the perspective of ensuring a healthy oral environment.

[0006] The present invention was made based on the above findings, and its object is to increase the concentration of S. oralis in the oral cavity.

[0007] The oral composition that solves the above problem is an oral composition containing an amino acid and a sugar, wherein the sugar is at least one selected from lactose, 2'-fucosyllactose, galactose, raffinose, and galactooligosaccharides.

[0008] In the oral cavity composition, the amino acid may be at least one selected from an acidic amino acid and an acidic amino acid salt.

[0009] One embodiment of the present invention will be described below. The oral composition of this embodiment contains a specific sugar and an amino acid. (Specific sugar) The specific sugar contained in the oral composition is at least one selected from lactose, 2'-fucosyllactose, galactose, raffinose, galactooligosaccharides, and hydrates thereof. The oral composition may contain only one of the specific sugars listed above, or may contain two or more of them in combination.

[0010] The content of the specific sugar in the oral composition is, for example, 0.5 to 4% by mass, preferably 1 to 3% by mass, and more preferably 1 to 2% by mass. (Amino Acids) The amino acids contained in the oral composition are not particularly limited. Examples of the amino acids include neutral amino acids such as alanine, proline, threonine, serine, valine, glycine, and citrulline; acidic amino acids and acidic amino acid salts such as aspartic acid and glutamic acid; and basic amino acids and basic amino acid salts such as lysine, arginine, and histidine. Specific examples of acidic amino acid salts include alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as magnesium salts and calcium salts. Specific examples of basic amino acid salts include hydrochlorides and sulfates.

[0011] The oral composition may contain only one of the above amino acids alone or a combination of two or more of them. It is particularly preferred that the oral composition contains at least one amino acid selected from acidic amino acids and acidic amino acid salts.

[0012] The content of the amino acid in the oral composition is, for example, 0.5 to 4% by mass, preferably 1 to 3% by mass, and more preferably 1.5 to 3% by mass. The mass ratio of the amino acid to the specific sugar in the oral composition (amino acid / specific sugar) is, for example, 0.25 to 4, preferably 0.5 to 3, and more preferably 1 to 2.

[0013] (Combination of specific sugar and specific amino acid) The oral composition preferably contains at least one selected from lactose, galactose, raffinose, and galactooligosaccharides as the specific sugar, and at least one selected from aspartic acid and aspartate as the specific amino acid. Furthermore, the oral composition preferably contains at least one selected from raffinose and galactooligosaccharides as the specific sugar, and at least one selected from glutamic acid and glutamate as the specific amino acid. Furthermore, the oral composition preferably contains galactose as the specific sugar, and citrulline as the specific amino acid. Furthermore, the oral composition preferably contains 2'-fucosyllactose as the specific sugar, and arginine as the specific amino acid.

[0014] (Application form, use, and dosage form) The application form of the oral composition is not particularly limited, and it can be used as, for example, a medicine, a quasi-drug, or a cosmetic. Known uses of the oral composition can be appropriately adopted, and examples thereof include toothpaste, mouthwash, gargle, liquid dentifrice, biofilm dispersant, anti-halitosis agent, gum massage agent, oral moisturizer, tongue coating remover, oral application agent, oral disinfectant, throat disinfectant, oral throat agent, periodontal disease treatment agent, denture wearing agent, denture coating agent, denture stabilizer, denture preservative, denture cleaner, and implant care agent.

[0015] The formulation of the oral composition is not particularly limited, and for example, by containing a solvent such as water or alcohol, it can be applied to ointments, pastes, sprays, gels, liquids, suspensions / emulsifiers, gums, etc.

[0016] The type of water used as a solvent is not particularly limited, and examples thereof include distilled water, pure water, ultrapure water, purified water, and tap water. The type of alcohol used as a solvent is not particularly limited, and examples thereof include ethanol. A mixture of water and alcohol can also be used.

[0017] When the oral composition is in a liquid form, the content of the solvent, such as water, is preferably 60 to 99.8% by mass, more preferably 70 to 90% by mass. The oral composition can be used as a bacterial growth-promoting composition for promoting the growth of S. oralis in the oral cavity. Examples of bacterial growth-promoting compositions include foods and beverages, as well as the aforementioned pharmaceuticals, quasi-drugs, and cosmetics.

[0018] The oral composition for use in foods and beverages can be used as various food ingredients or by adding it to beverage ingredients. The form of the food and beverage is not particularly limited and may be any of liquid, powder, gel, solid, etc. Specific examples include chewable tablets, lozenges, tablets, granules, powders, beverage powders, beverages, orally disintegrating films, oral sprays, and confectioneries such as chewing gum, candy, gummies, and jellies. The uses of the food and beverage are not particularly limited and may be applied as so-called general foods, health foods, functional foods, dietary supplements, supplements, foods for specified health uses, foods with functional claims, and foods for patients.

[0019] (Other Components) The oral composition may contain other components in addition to the components described above depending on the application purpose, form, use, etc. Examples of other components include antibacterial agents, anti-inflammatory agents, fragrances, humectants, surfactants, abrasives, alcohols, thickeners, sweeteners, medicinal components, colorants, stabilizers, and pH adjusters. Known components that are blended into oral compositions can be used as other components. The oral composition may contain only one of the above other components alone, or may contain two or more of them in combination.

[0020] Examples of antibacterial agents include cetylpyridinium chloride, paraben, sodium benzoate, triclosan, chlorhexidine hydrochloride, isopropylmethylphenol, benzalkonium chloride, benzethonium chloride, and hinokitiol.

[0021] Examples of anti-inflammatory agents include glycyrrhizinate, tranexamic acid, ε-aminocaproic acid, and Phellodendron bark extract. Examples of fragrances include anethole, eugenol, carvone, wintergreen, methyl salicylate, thymol, clove oil, sage oil, ocimene oil, and citronellol.

[0022] Examples of surfactants include nonionic surfactants, anionic surfactants, and amphoteric surfactants.Examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters and maltose fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters, sorbitan fatty acid esters such as sorbitan monolaurate, polyoxyethylene sorbitan monolaurate and polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, fatty acid alkanolamides such as lauric acid diethanolamide, polyoxyethylene stearyl ether and polyoxyethylene oleyl ether and other polyoxyethylene alkyl ethers, polyethylene glycol monooleate and polyethylene glycol monolaurate and other polyethylene glycol fatty acid esters, alkyl glucosides such as lauryl glucoside and decyl glucoside, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene fatty acid esters, alkyl glucosides, polyoxyethylene hydrogenated castor oil, glycerin fatty acid esters, and polyoxyethylene propylene block copolymers.

[0023] Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and polyoxyethylene lauryl ether sodium sulfate, sulfosuccinate salts such as sodium lauryl sulfosuccinate and polyoxyethylene lauryl ether sodium sulfosuccinate, acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine, and sodium cocoyl methyl taurate.

[0024] Examples of amphoteric surfactants include amino acid amphoteric surfactants such as N-lauryldiaminoethylglycine and N-myristyldiethylglycine, and betaine amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, N-alkyl-N'-carboxymethyl-N'-hydroxyethylethylenediamine salts, and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine.

[0025] Examples of abrasives include calcium carbonate, magnesium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, magnesium phosphate, silica, zeolite, sodium metaphosphate, aluminum hydroxide, magnesium hydroxide, calcium pyrophosphate, red iron oxide, calcium sulfate, and silicic anhydride.

[0026] Examples of alcohols include ethyl alcohol, lauryl alcohol, myristyl alcohol, etc. Examples of thickeners include sodium polyacrylate, carrageenan, sodium carboxymethylcellulose, sodium alginate, xanthan gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, and propylene glycol alginate.

[0027] Examples of medicinal ingredients include fluorides such as sodium monofluorophosphate, sodium fluoride, stannous fluoride, and strontium fluoride; condensed phosphates such as sodium pyrophosphate and sodium polyphosphate; phosphates such as sodium monohydrogen phosphate and trisodium phosphate; vitamins such as ascorbic acid, sodium ascorbate, pyridoxine hydrochloride, and tocopherol acetate; glucanase enzymes such as dextranase and mutanase; proteases; degradative enzymes such as lysozyme; inorganic salts such as zinc chloride, zinc citrate, strontium chloride, and potassium nitrate; chelating compounds such as chlorophyll and glycerophosphate; fat-dissolving polyethylene glycol; sodium chloride, aluminum lactate, and strontium chloride.

[0028] Examples of colorants include legally designated dyes such as Green No. 1, Blue No. 1, and Yellow No. 4, titanium oxide, etc. Examples of stabilizers include sodium edetate, sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, and magnesium sulfate.

[0029] Examples of pH adjusters include citric acid, malic acid, lactic acid, tartaric acid, acetic acid, phosphoric acid, pyrophosphoric acid, glycerophosphate, and various salts thereof such as potassium salts, sodium salts, and ammonium salts, sodium hydroxide, etc. The oral composition is preferably formulated with a pH adjuster to adjust the pH to a range of 4 to 9, particularly 5 to 7.

[0030] Next, the operation of this embodiment will be described. Although details are omitted, when the S. oralis concentration in saliva was compared between a group of subjects with a history of dental caries and a group of subjects without a history of dental caries, the group with no history of dental caries had a significantly higher S. oralis concentration. From this result, it is considered important to increase the S. oralis concentration in the oral cavity from the viewpoint of ensuring a healthy oral environment. The mechanism behind this can be speculated as follows.

[0031] Early colonizing bacteria are bacteria that adhere to tooth surfaces to form initial plaque and mediate the adhesion of pathogenic bacteria that form biofilms to tooth surfaces. Among early colonizing bacteria, S. oralis has weak adhesion to pathogenic bacteria that form biofilms, and areas on tooth surfaces where S. oralis has colonized are less likely to be affected by pathogenic bacteria than areas where other early colonizing bacteria have colonized.

[0032] Therefore, when the concentration of S. oralis in the oral cavity increases, the ratio of areas colonized by S. oralis to areas colonized by early-colonizing bacteria on the tooth surface increases. In other words, an increase in the concentration of S. oralis in the oral cavity competitively inhibits the colonization of other early-colonizing bacteria, which are likely to attract pathogenic bacteria, on the tooth surface. As a result of the inhibition of the colonization of other early-colonizing bacteria, which are likely to attract pathogenic bacteria, on the tooth surface, biofilm formation is suppressed, making it easier to achieve a healthy oral environment.

[0033] The oral composition of this embodiment allows S. oralis to grow in the oral cavity, and is expected to have the effect of suppressing biofilm formation based on the effect of allowing S. oralis to grow in the oral cavity.

[0034] Next, the effects of this embodiment will be described. (1) The oral composition contains an amino acid and a specific sugar. The specific sugar is at least one selected from lactose, 2'-fucosyllactose, galactose, raffinose, and galactooligosaccharides. This configuration allows S. oralis to grow in the oral cavity.

[0035] (2) The amino acid is at least one selected from an acidic amino acid and an acidic amino acid salt. In this case, the effect of promoting S. oralis in the oral cavity is more pronounced. (3) The specific sugar is at least one selected from lactose, galactose, raffinose, and galactooligosaccharides. The amino acid is at least one selected from aspartic acid and aspartate salts. In this case, the effect of promoting S. oralis in the oral cavity is more pronounced.

[0036] (4) The specific sugar is at least one selected from raffinose and galactooligosaccharide, and the amino acid is at least one selected from glutamic acid and glutamate. In this case, the effect of promoting the proliferation of S. oralis in the oral cavity is more pronounced.

[0037] The oral composition of the present invention will be described in more detail based on the following examples and comparative examples. However, the present invention is not limited to the configurations of the following examples. <Test 1> (Cultivation test of S. oralis) S. oralis was cultured in BHI medium (Brain Heart Infusion broth (manufactured by BD)). After measuring the turbidity of the culture solution at a wavelength of 660 nm, the culture solution was diluted with BHI medium so that the measured turbidity was 0.1, and this was used as a bacterial solution. Streptococcus oralis spp. tigurinus was used as S. oralis.

[0038] Sample solutions for the Examples and Comparative Examples were prepared by dissolving amino acids and sugars in BHI medium. The types of amino acids and sugars used in each sample solution are shown in Table 1. The amino acid concentration in each sample solution was 0 mg / ml or 15 mg / ml, and the sugar concentration was 20 mg / ml.

[0039] 100 μl of bacterial solution and 100 μl of sample solution were added to wells of a 96-well plate and cultured at 37°C under anaerobic conditions for 24 hours. After culture, the supernatant was removed, and 110 μl of Alamar Blue solution (Invitrogen) diluted 11-fold with phosphate-buffered saline (PBS) was added. Fluorescence intensity was measured at an excitation wavelength of 545 nm and a fluorescence wavelength of 590 nm. The relative fluorescence intensity of the control without sample solution was calculated as the growth degree of S. oralis, and the calculated growth degree was evaluated according to the following criteria. The results are shown in Table 1.

[0040] A: 10 or more B: 5 or more but less than 10 C: Less than 5

[0041]

[0042] As shown in Table 1, the growth of S. oralis was promoted when Examples 1 to 4, which used lactose monohydrate, galactose, raffinose, or galactooligosaccharide as the sugar and arginine as the amino acid, were added. On the other hand, the addition of Comparative Example 1, which contained no sugar, and Comparative Examples 2 to 7, which used isomaltooligosaccharide, fructooligosaccharide, inulin, xylitol, erythritol, or glycerin as the sugar, did not result in any effect of promoting the growth of S. oralis.

[0043] <Test 2> Next, lactose monohydrate, galactose, raffinose, and galactooligosaccharides, which showed growth-promoting effects in Test 1, were used as sugars, and the growth rate of S. oralis was measured when the type of amino acid was changed. The test method was the same as in Test 1. The types of amino acids and sugars used in each sample solution and the measurement results of the growth rate are shown in Table 2. In Test 2, the concentration of amino acids in each sample solution was 15 mg / ml only in Example 5, which used arginine, and 20 mg / ml in the other Examples.

[0044]

[0045] As shown in Table 2, the growth of S. oralis was promoted in all cases where Examples 5 to 23, which contained different types of amino acids, were added. The effect of promoting the growth of S. oralis was particularly significant when the acidic amino acid salts sodium aspartate or sodium glutamate were used as the amino acid. In particular, when galactose and sodium aspartate were combined, when raffinose and sodium aspartate or sodium glutamate were combined, and when galactooligosaccharides and sodium aspartate or sodium glutamate were combined, the growth rate reached 200 or more, and the growth of S. oralis was further promoted significantly. The results of Tests 1 and 2 indicate that the effect of promoting the growth of S. oralis is limited to the combination of a specific sugar and an arbitrary amino acid.

[0046] <Test 3> Next, the growth rate of S. oralis was measured when galactose was used as the sugar and citrulline was used as the amino acid. The test method was the same as in Test 1. The concentrations of galactose and citrulline in each sample solution and the measurement results of the growth rate are shown in Table 3. In Test 3, the galactose concentration in each sample solution was 0 mg / ml or 2 mg / ml, and the citrulline concentration was 0.5 to 3.0 mg / ml.

[0047]

[0048] As shown in Table 3, Comparative Example 8 is an example in which, of galactose and citrulline, only citrulline was contained, and the concentration of citrulline was varied. When each sample solution of Comparative Example 8 was added, the growth of S. oralis was promoted, but the effect of promoting growth decreased as the concentration of citrulline increased.

[0049] On the other hand, Example 24 is the example that contains both galactose and citrulline, and the concentration of galactose is constant, and the concentration of citrulline is changed.When adding each sample solution of Example 24, as the concentration of citrulline increases, the effect of promoting proliferation increases.In addition, when comparing the examples with the same concentration of citrulline, in all cases, the growth degree of Example 24 is higher than the growth degree of Comparative Example 8.

[0050] From the above results, it can be seen that the combined use of citrulline and galactose changes the effect of citrulline on the proliferation of S. oralis.Specifically, when citrulline is used alone, the promotion of S. oralis tends to decrease depending on the concentration of citrulline.When citrulline is used alone, the promotion of S. oralis tends to increase depending on the concentration of citrulline when used together with galactose.This result shows that citrulline and galactose do not affect the proliferation of S. oralis individually, but affect it together.

[0051] <Test 4> Next, the growth rate of S. oralis was measured when 2'-fucosyllactose was used as the sugar and arginine was used as the amino acid. The test method was the same as in Test 1. The concentrations of 2'-fucosyllactose and arginine in each sample solution and the measurement results of the growth rate are shown in Table 4. In Test 4, the concentration of 2'-fucosyllactose in each sample solution was 1 to 4 mg / ml, and the concentration of citrulline was 0 mg / ml or 1.5 mg / ml.

[0052]

[0053] As shown in Table 4, Comparative Example 9 is an example in which only 2'-fucosyllactose was contained among 2'-fucosyllactose and arginine, and the concentration of arginine was changed. When each sample solution of Comparative Example 9 was added, the effect of promoting the growth of S. oralis was hardly confirmed.

[0054] On the other hand, Example 25 contains both 2'-fucosyllactose and arginine, the arginine concentration is constant, and the 2'-fucosyllactose concentration is varied. When each sample solution of Example 25 was added, the effect of promoting the growth of S. oralis was confirmed. The effect of promoting the growth of S. oralis varied depending on the concentration of 2'-fucosyllactose. This result indicates that arginine alone does not affect the growth of S. oralis individually, but that 2'-fucosyllactose and arginine have a joint effect.

[0055] Next, the technical concept that can be understood from the above embodiment will be described below: (a) The oral composition, wherein the sugar is at least one selected from galactose, raffinose, and galactooligosaccharides, and the amino acid is at least one selected from aspartic acid and aspartate salts.

[0056] (b) The oral composition, wherein the sugar is at least one selected from raffinose and galactooligosaccharides, and the amino acid is at least one selected from glutamic acid and glutamate salts.

[0057] (c) The oral composition, wherein the mass ratio of the amino acid to the sugar (amino acid / sugar) is 0.5 to 4. (d) A bacterial growth-promoting composition that promotes the growth of Streptococcus oralis, comprising an amino acid and a sugar, wherein the sugar is at least one selected from lactose, galactose, raffinose, and galactooligosaccharides.

[0058] (e) A method for promoting bacterial growth, which promotes the growth of Streptococcus oralis in saliva, characterized by adding the bacterial growth-promoting composition to saliva.

Claims

1. A composition for promoting the growth of Streptococcus oralis, comprising an amino acid and a sugar, The composition, wherein the sugar is at least one selected from lactose, 2'-fucosyllactose, galactose, raffinose, and galactooligosaccharides.

2. The composition according to claim 1 , wherein the amino acid is at least one selected from the group consisting of acidic amino acids and acidic amino acid salts.

3. (i) the sugar comprises lactose, and the amino acid comprises at least one selected from arginine, aspartic acid, an aspartate salt, glutamic acid, a glutamate salt, lysine, and alanine; or (ii) the sugar comprises galactose, and the amino acid comprises at least one selected from arginine, aspartic acid, an aspartate salt, glutamic acid, a glutamate salt, and citrulline; (iii) the sugar contains raffinose, and the amino acid contains at least one selected from arginine, aspartic acid, an aspartate salt, glutamic acid, and a glutamate salt; (iv) the sugar comprises a galactooligosaccharide, and the amino acid comprises at least one selected from arginine, aspartic acid, an aspartate salt, glutamic acid, and a glutamate salt; (v) the sugar comprises 2'-fucosyllactose and the amino acid comprises arginine; (vi) the sugar is at least one selected from galactose, raffinose, and galactooligosaccharides, and the amino acid is at least one selected from aspartic acid and aspartate salts; or (vii) The composition according to claim 1, wherein the sugar is at least one selected from raffinose and galactooligosaccharides, and the amino acid is at least one selected from glutamic acid and glutamate salts.

4. A composition described in any one of claims 1 to 3, formulated as an oral composition.